Pervasive development disorders refer to a group of disorders characterized by delays in the development of multiple basic functions including socialization and communication. Pervasive developmental disorders include autism, Asperger syndrome, pervasive developmental disorder not otherwise specified (PDD-NOS), childhood disintegrative disorder, and Rett syndrome.
Rett Syndrome (RTT) is a pervasive developmental disorder that shares several clinical signs with autism but has an unrelated cause. RTT is caused by loss-of-function mutations in the gene encoding the methyl-CpG binding protein 2 (MeCP2), a transcriptional regulatory protein. After a period of apparently normal early postnatal development, RTT patients develop a spectrum of symptoms that generally includes loss of acquired speech, head growth deceleration, autistic behaviors, motor, respiratory and autonomic dysfunction and increased risk of seizures. Inactivation of Mepc2 at any age leads to RTT-like symptoms indicating that MeCP2 protein is required across the lifespan for normal brain function.
However, loss of MeCP2 in RTT patients and mouse models is not associated with neuronal cell death or axonal degeneration, although neurons are smaller, more densely packed than normal and exhibit reduced dendritic arborizations, spine density and synapse number. In addition, Mecp2 mutant mice exhibit defects in neuronal and synaptic function, including alterations in excitatory/inhibitory (E/I) balance. These microcircuit abnormalities are accompanied by altered expression of neurotransmitters, neurotransmitter synthesizing enzymes, receptors and transporters, as well as molecules required for synapse development.